Informations générales (source: ClinicalTrials.gov)
A Phase 1b Study of Bleximenib in Combination With AML-Directed Therapies for Participants With Acute Myeloid Leukemia Harboring KMT2A or NPM1 Alterations
Interventional
Phase 1
Janssen Research & Development, LLC (Voir sur ClinicalTrials)
octobre 2022
mars 2027
19 juillet 2025
The purpose of this study is to determine the recommended Phase 2 dose (RP2D)
candidate(s) of bleximenib in combination with AML directed therapies (dose selection)
and further to evaluate safety and tolerability of bleximenib in combination with AML
directed therapies at the RP2D(s) (dose expansion).
Etablissements
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CHU de Tours - Hôpital de Bretonneau - 37044 - Tours - France | Contact (sur clinicalTrials) | ||||
| Chu Rennes Hopital Pontchaillou - 35033 - Rennes Cedex 9 - France | Contact (sur clinicalTrials) | ||||
| Institut Paoli Calmettes - 13273 - Marseille Cedex 9 - France | Contact (sur clinicalTrials) | ||||
| Institut Universitaire du Cancer Toulouse Oncopole - 31100 - Toulouse Cedex 9 - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Adolescent participants (defined as greater than or equal to [>=] 12 and less than
[<] 18 years of age) are only eligible for the relapsed/refractory (R/R) cohort (Arm
A, cohort A4)
- Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo
or secondary AML; b) relapsed/refractory (Arm A only); c) harboring KMT2A, NPM1,
NUP98, or NUP214 alterations; d) Participants may receive emergency leukapheresis
and/or cytarabine as cytoreductive therapy according to local practice guidelines
- Pretreatment clinical laboratory values meeting the following criteria -listed
below: White blood cell (WBC) count: less than or equal to (<=) 25*10^9 per liter
(/L), adequate liver and renal function
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2.
Adolescent participants only: Performance status >70 by Lansky scale (for
participants <16 years of age) or >70 Karnofsky scale (for participants >16 years of
age)
- A female of childbearing potential must have a negative highly sensitive serum
beta-human chorionic gonadotropin at screening and within 48 hours prior to the
first dose of study treatment
- Must sign an informed consent form (ICF) indicating participant (or their legally
authorized representative) understands the purpose of the study and procedures
required for the study and is willing to participate in the study
- Willing and able to adhere to the prohibitions and restrictions specified in this
protocol
- Adolescent participants (defined as greater than or equal to [>=] 12 and less than
[<] 18 years of age) are only eligible for the relapsed/refractory (R/R) cohort (Arm
A, cohort A4)
- Diagnosis of AML according to World Health Organization (WHO) criteria: a) De novo
or secondary AML; b) relapsed/refractory (Arm A only); c) harboring KMT2A, NPM1,
NUP98, or NUP214 alterations; d) Participants may receive emergency leukapheresis
and/or cytarabine as cytoreductive therapy according to local practice guidelines
- Pretreatment clinical laboratory values meeting the following criteria -listed
below: White blood cell (WBC) count: less than or equal to (<=) 25*10^9 per liter
(/L), adequate liver and renal function
- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0, 1 or 2.
Adolescent participants only: Performance status >70 by Lansky scale (for
participants <16 years of age) or >70 Karnofsky scale (for participants >16 years of
age)
- A female of childbearing potential must have a negative highly sensitive serum
beta-human chorionic gonadotropin at screening and within 48 hours prior to the
first dose of study treatment
- Must sign an informed consent form (ICF) indicating participant (or their legally
authorized representative) understands the purpose of the study and procedures
required for the study and is willing to participate in the study
- Willing and able to adhere to the prohibitions and restrictions specified in this
protocol
- Acute promyelocytic leukemia, diagnosis of Down syndrome associated leukemia or
juvenile myelomonocytic leukemia according to WHO 2016 criteria
- Leukemic involvement of the central nervous system
- Recipient of solid organ transplant
- Cardiovascular disease that is uncontrolled, increases risk for Torsades de Pointes
or that was diagnosed within 6 months prior to the first dose of study treatment
including, but not limited to: (a) Myocardial infarction; (b) Severe or unstable
angina; (c) Clinically significant cardiac arrhythmias, including bradycardia (<50
beats per minute); (d) Uncontrolled (persistent) hypertension: (example, blood
pressure greater than [>] 140/90 millimeters of mercury [mm Hg]; (e) Acute
neurologic events such as stroke or transient ischemic attack, intracranial or
subarachnoid hemorrhage, intracranial trauma; (f) Venous thromboembolic events
(example, pulmonary embolism) within 1 month prior to the first dose of study
treatment ;(g) Congestive heart failure (NYHA class III to IV); (h) Pericarditis or
clinically significant pericardial effusion; (i) Myocarditis; (j) Endocarditis (k)
Clinically significant hypokalemia, hypomagnesemia, hypocalcemia (corrected for
hypoalbuminemia)
- Any toxicity (except for alopecia, stable peripheral neuropathy, thrombocytopenia,
neutropenia, anemia) from previous anticancer therapy that has not resolved to
baseline or to grade 1 or less
- Pulmonary compromise that requires the need for supplemental oxygen use to maintain
adequate oxygenation
- Participants with diagnosis of Fanconi anemia, Kostmann syndrome, Shwachman diamond
syndrome, or any other known bone marrow failure syndrome